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1.
Eur Arch Paediatr Dent ; 22(3): 507-513, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33389688

ABSTRACT

PURPOSE: The UK government introduced a nationwide lockdown on the 23rd March 2020 to prevent the spread of COVID-19. All elective hospital and dental practice assessments and procedures were mandated to stop. Key hospital dental workers were required to work, and Guy's and St Thomas' NHS Foundation Trust became a designated Urgent Dental Care Centre (UDC) for the greater London area. The paediatric dental emergency walk-in service was suspended and replaced with a telephone triage system and evaluation of digital images sent by parents/carers when needed. The aim of this paper is to describe the emergency service provided by staff in the department of Paediatric Dentistry at St Thomas' Hospital during the first lockdown. METHODS: A prospective service evaluation of the modified paediatric dental emergency service was carried out between 25th March and 29th May 2020. RESULTS: Four-hundred and sixty-four patients accessed the paediatric dental emergency service via telephone during the service evaluation period. Of these, 192 (41%) had dental pain, 121 (26%) had pain and swelling of dental origin, and 89 (19%) had trauma. CONCLUSIONS: Remote telephone consultations and digital photographs were useful to screen emergency paediatric dental patients, but lack of face-to-face consultations with radiographic assessment and access to general anaesthetic services were major limiting factors.


Subject(s)
COVID-19 , Pandemics , Child , Communicable Disease Control , Emergency Service, Hospital , Humans , London/epidemiology , Prospective Studies , SARS-CoV-2
4.
Br Dent J ; 223(10): 745, 2017 11 24.
Article in English | MEDLINE | ID: mdl-29171522

Subject(s)
Oral Health , Smoking
6.
J Labelled Comp Radiopharm ; 59(4): 175-86, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26991121

ABSTRACT

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

8.
Bone Marrow Transplant ; 47(1): 40-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21358684

ABSTRACT

Haematopoietic SCT (HSCT) is curative for many children with primary immunodeficiencies or other non-malignant conditions. Outcome for those admitted to intensive care following HSCT for oncology diagnoses has historically been very poor. There is no literature available specifically regarding the outcome for children with primary immunodeficiency requiring intensive care following HSCT. We reviewed our post-HSCT admission to intensive care over a 5-year period. A total of 111 children underwent HSCT. Median age at transplant was 1 year 4 months. The most common diagnosis was SCID. In all, 35% had at least one intensive care admission and 44% survived to be discharged from intensive care. Also, 73% of admission episodes requiring invasive ventilation but no inotropes or renal replacement therapy resulted in survival to discharge. Children undergoing HSCT for immunological diagnoses had a high rate of admission to intensive care. No factors were identified that could predict the need for admission. Invasive ventilation alone has a much better outcome than that in historical series. However, the need for multi-organ system support was still associated with a poor outcome. This information is useful when counselling families of children that have deteriorated and been admitted to intensive care during the HSCT procedure.


Subject(s)
Critical Care/methods , Hematopoietic Stem Cell Transplantation , Severe Combined Immunodeficiency/mortality , Severe Combined Immunodeficiency/therapy , Adolescent , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Humans , Infant , Male , Survival Rate , Transplantation, Homologous
9.
Clin Immunol ; 137(3): 357-65, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20832369

ABSTRACT

Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαß+CD4-CD8- double negative T cells and impaired T cell apoptosis are hallmarks of the disease. In contrast, the B cell compartment has been less well studied. We found an altered distribution of B cell subsets with raised transitional B cells and reduced marginal zone B cells, switched memory B cells and plasma blasts in most of 22 analyzed ALPS patients. Moreover, 5 out of 66 ALPS patients presented with low IgG and susceptibility to infection revealing a significant overlap between ALPS and common variable immunodeficiency (CVID). In patients presenting with lymphoproliferation, cytopenia, hypogammaglobulinemia and impaired B cell differentiation, serum biomarkers were helpful in addition to apoptosis tests for the identification of ALPS patients. Our observations may indicate a role for apoptosis defects in some diseases currently classified as CVID.


Subject(s)
Autoimmune Lymphoproliferative Syndrome/diagnosis , Autoimmune Lymphoproliferative Syndrome/immunology , B-Lymphocytes/immunology , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/immunology , Fas Ligand Protein/blood , Interleukin-10/blood , Vitamin B 12/blood , Adolescent , Adult , Agammaglobulinemia/immunology , Apoptosis , Biomarkers/blood , Child , Child, Preschool , Diagnosis, Differential , Fas Ligand Protein/immunology , Flow Cytometry , Humans , Immunoglobulin G/blood , Interleukin-10/immunology , Middle Aged , Monocytes/immunology , Phenotype , T-Lymphocytes/immunology , Vitamin B 12/immunology , fas Receptor/blood , fas Receptor/immunology
10.
Clin Exp Immunol ; 156(1): 40-51, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19196253

ABSTRACT

Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1-10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.


Subject(s)
Candidiasis, Chronic Mucocutaneous/immunology , Polyendocrinopathies, Autoimmune/immunology , Receptors, Pattern Recognition/blood , Candida albicans/immunology , Candidiasis, Chronic Mucocutaneous/genetics , Cell Differentiation/immunology , Cells, Cultured , Dendritic Cells/immunology , Female , Gene Expression Regulation/immunology , Humans , Lipopolysaccharides/immunology , Male , Monocytes/immunology , Mutation , Polyendocrinopathies, Autoimmune/genetics , Polymerase Chain Reaction/methods , RNA, Messenger/genetics , Receptors, Pattern Recognition/biosynthesis , Receptors, Pattern Recognition/genetics , Signal Transduction/immunology , Transcription Factors/genetics , AIRE Protein
11.
Clin Exp Immunol ; 154(3): 406-14, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19037923

ABSTRACT

Patients with chronic mucocutaneous candidiasis (CMC) suffer persistent infections with the yeast Candida. CMC includes patients with autoimmune regulator (AIRE) gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, and dendritic cells (DCs), as central orchestrators, may underlie pathogenic disease mechanisms. In 29 patients with CMC (13 with APECED) and controls, we generated monocyte-derived DCs, stimulated them with Candida albicans, Toll-like receptor-2/6 ligand and lipopolysaccharide to assess cytokine production [interleukin (IL)-12p70, IL-23, interferon (IFN)-gamma, IL-2, tumour necrosis factor (TNF)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-5, IL-13] and cell-surface maturation marker expression (CD83, CD86, human leucocyte antigen D-related). In both APECED and non-APECED CMC patients, we demonstrate impairment of DC function as evidenced by altered cytokine expression profiles and DC maturation/activation: (1) both groups over-produce IL-2, IFN-gamma, TNF-alpha and IL-13 and demonstrate impaired DC maturation. (2) Only non-APECED patients showed markedly decreased Candida-stimulated production of IL-23 and markedly increased production of IL-6, suggesting impairment of the IL-6/IL-23/T helper type 17 axis. (3) In contrast, only APECED patients showed DC hyperactivation, which may underlie altered T cell responsiveness, autoimmunity and impaired response to Candida. We demonstrate different pathogenic mechanisms on the same immune response pathway underlying increased susceptibility to Candida infection in these patients.


Subject(s)
Candidiasis, Chronic Mucocutaneous/immunology , Cytokines/biosynthesis , Dendritic Cells/immunology , Polyendocrinopathies, Autoimmune/immunology , Adolescent , Adult , Cell Differentiation/immunology , Cells, Cultured , Child , Child, Preschool , Disease Susceptibility , Female , Humans , Inflammation Mediators/metabolism , Interleukin-23/biosynthesis , Male , Middle Aged , Th1 Cells/immunology , Th2 Cells/immunology , Young Adult
12.
Clin Exp Immunol ; 153(1): 75-80, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18505430

ABSTRACT

More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T-B + NK + SCID phenotype. Severe immunodeficiency with CHARGE syndrome has been noted only rarely Omenn syndrome is a rare autosomal recessive form of SCID with erythroderma, hepatosplenomegaly, lymphadenopathy and alopecia. Hypomorphic recombination activating genes 1 and 2 mutations were first described in patients with Omenn syndrome. More recently, defects in Artemis, RMRP, IL7Ralpha and common gamma chain genes have been described. We describe four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T-B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients). Immunodeficiency in patients with DiGeorge syndrome is well recognized--CHARGE syndrome should now be added to the causes of T-B + NK + SCID, and mutations in the CHD7 gene may be associated with Omenn-like syndrome.


Subject(s)
B-Lymphocytes/immunology , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Mutation , Severe Combined Immunodeficiency/genetics , T-Lymphocytes/immunology , Disease Progression , Female , Genotype , Humans , Infant , Infant, Newborn , Killer Cells, Natural/immunology , Male , Syndrome , Thymus Gland/abnormalities
13.
Clin Exp Immunol ; 152(2): 211-8, 2008 May.
Article in English | MEDLINE | ID: mdl-18410635

ABSTRACT

There are no epidemiological studies from the British Isles of chronic granulomatous disease, characterized by recurrent, life-threatening bacterial and fungal infections and inflammatory sequelae. Patients were enrolled in a national registry and medical records were analysed. Of 94 subjects, 69 had X-linked disease, 16 had autosomal recessive disease and nine were unknown. Prevalence was 7.5/million for 1990-99 and 8.5/million for 1980-89. Suppurative adenitis, abscesses and pneumonia presented commonly. Twenty-three of 30 patients who underwent high resolution computerized tomography had chronic respiratory disease. Inflammatory sequelae included bowel stricture and urogenital tract granulomata. Growth failure was common; 75% of those measured were below the population mean. All patients received prophylactic antibiotics and 93% anti-fungal prophylaxis. Interferon gamma was used to treat infection, but rarely as prophylaxis. Despite prophylaxis, estimated survival was 88% at 10 years but 55% at age 30 years. Morbidity remains significant, severe infectious complications common. Curative treatments including stem cell transplantation should be considered for patients with frequent or serious complications.


Subject(s)
Granulomatous Disease, Chronic/epidemiology , Adolescent , Adult , Aspergillosis/complications , Aspergillosis/epidemiology , Child , Child, Preschool , Epidemiologic Methods , Female , Granulomatous Disease, Chronic/complications , Humans , Infant , Infant, Newborn , Ireland/epidemiology , Male , Middle Aged , Opportunistic Infections/complications , Opportunistic Infections/epidemiology , Respiratory Tract Infections/complications , Respiratory Tract Infections/epidemiology , Staphylococcal Infections/complications , Staphylococcal Infections/epidemiology , United Kingdom/epidemiology
15.
Arch Dis Child ; 93(3): 200-3, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17350970

ABSTRACT

OBJECTIVE: Assays based on interferon gamma (IFNgamma) are an exciting new development for screening for latent tuberculosis infection (LTBI) in adults, but there are limited data on their effectiveness in children. Nevertheless new National Institute for Health and Clinical Excellence (NICE) guidelines recommend their use when screening paediatric tuberculosis (TB) contacts. We evaluated the potential effect of the new NICE guidelines on current paediatric practice. DESIGN: Children screened for TB who had had an IFNgamma assay performed (QuantiFERON-TB Gold (QFG)) were included. Actual outcomes from existing guidelines were compared with those that would have been obtained using NICE guidelines. RESULTS: QFG assays were performed on 120 children, 103 as part of TB contact tracing. Six of the 120 (5%) were QFG positive, and seven of the 120 (6%) were indeterminate. Where both Mantoux and QFG results were available, these agreed in 62/104 (60%) of cases. QFG tests were more likely to correlate with a negative Mantoux (98% agreement) than with a positive Mantoux (11% agreement). Management outcomes differed for 23/103 children seen as part of TB contact tracing. Only one (1%) of these had an indeterminate QFG result. 17 (85%) fewer children would have been given LTBI treatment (chemoprophylaxis) and two (2%) children with possible TB would not have been identified using NICE guidelines. CONCLUSION: New NICE guidelines for the use of IFNgamma-based tests for TB screening will reduce the number of children treated for presumed LTBI. Long-term prospective studies are needed to determine the number of children with positive Mantoux tests but negative IFNgamma results who are not given LTBI treatment yet later develop TB.


Subject(s)
Mass Screening/methods , Practice Guidelines as Topic , Tuberculosis/diagnosis , Adolescent , Child , Child, Preschool , England , Enzyme-Linked Immunosorbent Assay , Humans , Infant , Interferon-gamma/blood , Tuberculin Test/methods
16.
J Med Genet ; 45(2): 93-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17893117

ABSTRACT

BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. RESULTS AND CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.


Subject(s)
Chromosomal Instability , Craniofacial Abnormalities/genetics , Immunologic Deficiency Syndromes/genetics , Adolescent , Adult , Centromere/genetics , Child , Child, Preschool , Craniofacial Abnormalities/pathology , DNA (Cytosine-5-)-Methyltransferases/genetics , Female , Genotype , Humans , Infant , Male , Mutation , Phenotype , Syndrome , DNA Methyltransferase 3B
17.
Bone Marrow Transplant ; 40(6): 529-33, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17637688

ABSTRACT

Pulmonary infection, often insidious, is frequent in primary immunodeficiency (PID) and acquired immunodeficiency. Pulmonary complications are serious obstacles to success of haematopoietic SCT (HSCT) for these conditions. Bronchoalveolar lavage (BAL) permits identification of lower respiratory tract pathogens that may direct specific treatment and influence prognosis. There are no reports about the utility of pre-HSCT BAL for immunodeficient patients. We prospectively studied the value of 'routine' BAL before commencing transplantation in patients undergoing HSCT for severe immunological disease. Routine non-bronchoscopic BAL was performed under general anaesthetic, a few days before commencing pre-HSCT cytoreductive chemotherapy. Patients were categorized as symptomatic or asymptomatic with respect to pulmonary disease or infection. Samples were sent for microbiological processing. Complications arising from the procedure, pathogens isolated and treatments instituted were recorded. Results were available from 69/75 patients transplanted during the study period; 26 (38%) had pathogens identified (six asymptomatic patients), 10 (14.5%) developed complications post-procedure (two asymptomatic patients)-all recovered, 21 had management changes. There was no statistically significant difference in the number of positive isolates from severe combined or other immunodeficient patients, or of symptomatic or asymptomatic patients. Routine non-bronchoscopic BAL is safe in immunodeficient patients about to undergo HSCT, and leads to management changes.


Subject(s)
Autoimmune Diseases/therapy , Bronchoalveolar Lavage , Hematopoietic Stem Cell Transplantation , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/diagnosis , Severe Combined Immunodeficiency/therapy , Adolescent , Anesthesia, General , Autoimmune Diseases/complications , Bronchoalveolar Lavage Fluid/microbiology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/immunology , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/immunology , Prognosis , Prospective Studies , Severe Combined Immunodeficiency/complications
18.
Pediatr Blood Cancer ; 47(3): 332-4, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16007596

ABSTRACT

Wiskott-Aldrich syndrome, an X-linked primary immunodeficiency can be cured by bone marrow transplantation. Umbilical cord haemopoietic stem cells are increasingly used as an alternative to bone marrow; advantages include ready availability, no risk to the donor, low rate of viral contamination, and low risk of graft versus host disease. Disadvantages include low stem cell dose for larger patients and lack of stem cells for boost infusions following the initial procedure. We report the case of a child with Wiskott-Aldrich syndrome who underwent cord blood stem cell transplantation with two separate cord blood units, 8 days apart.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Stem Cell Transplantation , Wiskott-Aldrich Syndrome/therapy , Humans , Infant , Male , Risk Factors , Stem Cell Transplantation/adverse effects , Treatment Outcome
19.
Bone Marrow Transplant ; 36(4): 295-9, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15968287

ABSTRACT

Primary immunodeficiencies (PID) are an important cause of childhood mortality. Haematopoietic stem cell transplantation (HSCT) is the best treatment for many PID. Umbilical cord stem cells are an alternative source of HSC. There is little data regarding outcome of umbilical cord stem cell transplantation (UCSCT) for PID. Our single centre experience is reported. A retrospective study of 14 of 148 patients transplanted for PID, who have received 15 UCSCT was performed, with specific regard to graft-versus-host disease (GvHD) and immune reconstitution. Eight patients with severe combined immunodeficiency (SCID), and six with other combined immunodeficiencies were treated. Of the patients, 12 received unrelated cords, and two had sibling transplants. Median age at transplant was 3.5 months, median nucleated cell dose was 0.8 x 10(8)/kg. All engrafted. Median time to neutrophil engraftment was 22 days, median time to platelet engraftment was 51 days. One developed significant grade III GvHD post transplantation. In total, 11 patients had full donor T and six full donor B-cell chimerism, six of nine patients >1 year post-BMT had normal IgG levels and specific antibody responses to tetanus and Hib vaccines; two are being assessed. Two patients died of multi-organ failure related to pre-existing infection and inflammatory complications respectively. UCSCT should be considered for patients requiring stem cell therapy for PID.


Subject(s)
Immunologic Deficiency Syndromes/therapy , Antibody Formation , B-Lymphocytes , Child, Preschool , Cord Blood Stem Cell Transplantation , Female , Graft Survival , Graft vs Host Disease , Humans , Immune System/cytology , Immune System/physiology , Immunoglobulin G/blood , Infant , Male , Regeneration , Retrospective Studies , T-Lymphocytes , Transplantation Chimera , Treatment Outcome
20.
Clin Exp Immunol ; 140(2): 289-92, 2005 May.
Article in English | MEDLINE | ID: mdl-15807853

ABSTRACT

This observational study describes the ranges observed for lymphocyte subsets for significantly preterm infants (<32 weeks) in the first year of life, measured by single platform flow cytometry and compared to identically determined subsets in term infants. After ethical approval 39 term and 28 preterm infants had lymphocyte subset analysis before and after their primary immunization series. Median values with 5th and 95th percentiles of absolute counts and percentages are presented for total lymphocytes, T cells, NK cells, B cells, cytotoxic T cells, helper T cells, dual positive T cells, activated T cells, activated T helper cells (including T regulatory cells), pan memory T cells, pan naive T cells, memory helper T cells, naive helper T cells and the T helper/suppressor ratio. The lymphocyte profile of the preterm infants differed from that of the term infants.


Subject(s)
Infant, Premature/immunology , Lymphocyte Subsets/immunology , Birth Weight , Female , Flow Cytometry/methods , Humans , Immunization , Infant, Newborn/immunology , Killer Cells, Natural/immunology , Lymphocyte Count , Male , T-Lymphocytes, Helper-Inducer/immunology
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